dbSNP rs779432585: DAB1:p.Pro536Ser (chr1-57010757-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365792.1(DAB1):c.1606C>T(p.Pro536Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P536A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DAB1
NM_001365792.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.07

Publications

0 publications found

Variant links:

Genes affected

DAB1 (HGNC:2661): (DAB adaptor protein 1) The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

DAB1 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 37
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

DAB1 links:

LOC112267900 (HGNC:):

LOC112267900 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2614273).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365792.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAB1	NM_001365792.1	MANE Select	c.1606C>T	p.Pro536Ser	missense	Exon 14 of 15	NP_001352721.1	O75553-6
DAB1	NM_001353983.2		c.1606C>T	p.Pro536Ser	missense	Exon 14 of 15	NP_001340912.1	O75553-6
DAB1	NM_001353985.2		c.1606C>T	p.Pro536Ser	missense	Exon 14 of 15	NP_001340914.1	O75553-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAB1	ENST00000371236.7	TSL:5 MANE Select	c.1606C>T	p.Pro536Ser	missense	Exon 14 of 15	ENSP00000360280.1	O75553-6
DAB1	ENST00000420954.6	TSL:1	c.1600C>T	p.Pro534Ser	missense	Exon 13 of 14	ENSP00000395296.2	O75553-5
DAB1	ENST00000371231.5	TSL:5	c.1705C>T	p.Pro569Ser	missense	Exon 15 of 15	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1444534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716314

African (AFR)

AF:

0.00

AC:

AN:

32864

American (AMR)

AF:

0.00

AC:

AN:

43234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25698

East Asian (EAS)

AF:

0.00

AC:

AN:

39230

South Asian (SAS)

AF:

0.00

AC:

AN:

84142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101030

Other (OTH)

AF:

0.00

AC:

AN:

59510

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.20

PhyloP100

4.1

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.13

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.019

Polyphen

0.95

Vest4

0.39

MutPred

0.29

Gain of phosphorylation at P569 (P = 0.0035)

MVP

0.70

MPC

0.34

ClinPred

0.81

GERP RS

5.0

Varity_R

0.23

gMVP

0.55

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over